“In vivo” local transfection of a cis element decoy mimicking an estrogen receptor alpha gene promoter region induces apoptosis of osteoclasts following application of orthodontic forces to rat teeth

Abstract

We have recently reported that it is possible to induce apoptosis of human primary osteoclasts (OCs) following a transcription factor decoy (TFD) approach specifically designed for increasing the expression of the human estrogen receptor alpha (ERα) gene [1]. ERα expression was increased by interfering with the activity of a negative transcription factor and by removing it with a powerful TFD oligonucleotide (ODN, named RA4-3′) mimicking a region of the distal promoter C of ERα gene. The RA4-3′ mediated induction of OCs apoptosis was also associated with increase of the levels of caspase 3 and Fas receptor [1]. From the theoretical point of view, our published study confirmed a role of ERα on osteoclastic cell function. From the practical point of view, we proposed this TFD approach for the therapy of diseases caused by OCs activation. In order to demonstrate the efficacy of our strategy “in vivo”, we employed an experimental model system constituted by rats subjected to orthodontic forces inducing alveolar bone resorption during orthodontic tooth movement [2]. This system is very useful for